Entropic transport: kinetics, scaling, and control mechanisms

We show that transport in the presence of entropic barriers exhibits peculiar characteristics which makes it distinctly different from that occurring through energy barriers. The constrained dynamics yields a scaling regime for the particle current and the diffusion coefficient in terms of the ratio between the work done to the particles and available thermal energy. This interesting property, genuine to the entropic nature of the barriers, can be utilized to effectively control transport through quasi-one-dimensional structures in which irregularities or tortuosity of the boundaries cause entropic effects. The accuracy of the kinetic description has been corroborated by simulations. Applications to different dynamic situations involving entropic barriers are outlined.

Vertical Clearance Restrictions on Primary Roads and Primary Road Extensions: Standard U.S. Measurements [Vertical Clearance Log], May 1, 2015

The Vertical Clearance Log is prepared for the purpose of providing vertical clearance restrictions by route on the primary road system. This report is used by the Iowa Department of Transportation’s Motor Carrier Services to route oversize vehicles around structures with vertical restrictions too low for the cargo height. The source of the data is the Geographic Information Management System (GIMS) that is managed by the Office of Research & Analytics in the Performance & Technology Division. The data is collected by inspection crews and through the use of LiDAR technology to reflect changes to structures on the primary road system. This log is produced annually.

Characterization of cerebral glucose dynamics in vivo with a four-state conformational model of transport at the blood-brain barrier.

Determination of brain glucose transport kinetics in vivo at steady-state typically does not allow distinguishing apparent maximum transport rate (T(max)) from cerebral consumption rate. Using a four-state conformational model of glucose transport, we show that simultaneous dynamic measurement of brain and plasma glucose concentrations provide enough information for independent and reliable determination of the two rates. In addition, although dynamic glucose homeostasis can be described with a reversible Michaelis-Menten model, which is implicit to the large iso-inhibition constant (K(ii)) relative to physiological brain glucose content, we found that the apparent affinity constant (K(t)) was better determined with the four-state conformational model of glucose transport than with any of the other models tested. Furthermore, we confirmed the utility of the present method to determine glucose transport and consumption by analysing the modulation of both glucose transport and consumption by anaesthesia conditions that modify cerebral activity. In particular, deep thiopental anaesthesia caused a significant reduction of both T(max) and cerebral metabolic rate for glucose consumption. In conclusion, dynamic measurement of brain glucose in vivo in function of plasma glucose allows robust determination of both glucose uptake and consumption kinetics.

Regulation of sodium transport in the cortical collecting duct : physiological role of GILZ in vitro and in vivo : characterisation of Na+ transport in the mCCDcl1 cell line

SUMMARY Regulation of sodium excretion by the kidney is a key mechanism in the long term regulation of blood pressure, and when altered it constitutes a risk factor for the appearance of arterial hypertension. Aldosterone, which secretion depends upon salt intake in the diet, is a steroid hormone that regulates sodium reabsorption in the distal part of the nephron (functional unit of the kidney) by modulating gene transcription. It has been shown that it can act synergistically with the peptidic hormone insulin through the interaction of their signalisation pathways. Our work consisted of two distinct parts: 1) the in vitro and in vivo characterisation of Glucocorticoid-Induced Leucine Zipper (GILZ) (an aldosterone-induced gene) mechanism of action; 2) the in vitro characterisation of insulin mechanism of action and its interaction with aldosterone. GILZ mRNA, coded by the TSC22D3 gene, is strongly induced by aldosterone in the cell line of principal cells of the cortical collecting duct (CCD) mpkCCDc14, suggesting that GILZ is a mediator of aldosterone response. Co-expression of GILZ and the amiloride-sensitive epithelial sodium channel ENaC in vitro in the Xenopus oocyte expression system showed that GILZ has no direct effect on the ENaC-mediated Na+ current in basal conditions. To define the role of GILZ in the kidney and in other organs (colon, heart, skin, etc.), a conditional knock-out mouse is being produced and will allow the in vivo study of its role. Previous data showed that insulin induced a transepithelial sodium transport at supraphysiological concentrations. Insulin and the insulin-like growth factor 1 (IGF-1) are able to bind to each other receptor with an affinity 50 to 100 times lower than to their cognate receptor. Our starting hypothesis was that the insulin effect observed at these supraphysiological concentrations is actually mediated by the IGF receptor type 1 (IGF-1R). In a new cell line that presents all the characteristics of the principal cells of the CCD (mCCDc11) we have shown that both insulin and IGF-1 induce a physiologically significant increase of Na+ transport through the activation of IGF-1R. Aldosterone and insulin/IGF-1 have an additive effect on Na+ transport, through the activation of the PI3-kinase (PI3-K) pathway and the phosphorylation of the serum- and glucocorticoid-induced kinase 1 (Sgk1) by the IGF-1R, and the induction of Sgk1 expression by aldosterone. Thus, Sgk1 integrates IGF-1/insulin and aldosterone effects. We suggest that IGF-1 is physiologically relevant in the modulation of sodium balance, while insulin can only regulate Na+ transport at supraphysiological conditions. Both hormones would bind to the IGF-1R and induce Na+ transport by activating the PI3-K PDK1/2 - Sgk1 pathway. We have shown for the first time that Sgk1 is expressed and phosphorylated in principal cells of the CCD in basal conditions, although the mechanism that maintains Sgk1 phosphorylation is not known. This new role for IGF-1 suggests that it could be a salt susceptibility gene. In effect, IGF-1 stimulates Na+ and water transport in the kidney in vivo. Moreover, 35 % of the acromegalic patients (overproduction of growth hormone and IGF-1) are hypertensives (higher proportion than in normal population), and genetic analysis suggest a link between the IGF-1 gene locus and blood pressure. RÉSUMÉ La régulation de l'excrétion rénale de sodium (Na+) joue un rôle principal dans le contrôle à long terme de la pression sanguine, et ses altérations constituent un facteur de risque de l'apparition d'une hypertension artérielle. L'aldosterone, dont la sécrétion dépend de l'apport en sel dans la diète, est une hormone stéroïdienne qui régule la réabsorption de Na+ dans la partie distale du nephron (unité fonctionnelle du rein) en contrôlant la transcription de gènes. Elle peut agir de façon synergistique avec l'hormone peptidique insuline, probablement via l'interaction de leurs voies de signalisation cellulaire. Le but de notre travail comportait deux volets: 1) caractériser in vitro et in vivo le mécanisme d'action du Glucocorticoid Induced Leucine Zipper (GILZ) (un gène induit par l'aldosterone); 2) caractériser in vitro le mécanisme d'action de l'insuline et son interaction avec l'aldosterone. L'ARNm de GILZ, codé par le gène TSC22D3, est induit par l'aldosterone dans la lignée cellulaire de cellules principales du tubule collecteur cortical (CCD) mpkCCDc14, suggérant que GILZ est un médiateur potentiel de la réponse à l'aldosterone. La co-expression in vitro de GILZ et du canal à Na+ sensible à l'amiloride ENaC dans le système d'expression de l'oocyte de Xénope a montré que GILZ n'a pas d'effet sur les courants sodiques véhiculées par ENaC en conditions basales. Une souris knock-out conditionnelle de GILZ est en train d'être produite et permettra l'étude in vivo de son rôle dans le rein et d'autres organes. Des expériences préliminaires ont montré que l'insuline induit un transport transépithelial de Na+ à des concentrations supraphysiologiques. L'insuline et l'insulin-like growth factor 1 (IGF-1) peuvent se lier à leurs récepteurs réciproques avec une affinité 50 à 100 fois moindre qu'à leur propre récepteur. Nous avons donc proposé que l'effet de l'insuline soit médié par le récepteur à l'IGF type 1 (IGF-1R). Dans une nouvelle lignée cellulaire qui présente toutes les caractéristiques des cellules principales du CCD (mCCDc11) nous avons montré que les deux hormones induisent une augmentation physiologiquement significative du transport du Na+ par l'activation des IGF-1 R. Aldosterone et insuline/IGF-1 ont un effet additif sur le transport de Na+, via l'activation de la voie de la PI3-kinase et la phosphorylation de la serum- and glucocorticoid-induced kinase 1 (Sgk1) par l'IGF-1R, dont l'expression est induite par l'aldosterone. Sgk1 intègre les effets de l'insuline et l'aldosterone. Nous proposons que l'IGF-1 joue un rôle dans la modulation physiologique de la balance sodique, tandis que l'insuline régule le transport de Na+ à des concentrations supraphysiologiques. Les deux hormones agissent en se liant à l'IGF-1R et induisent le transport de Na+ en activant la cascade de signalisation PI3-K - PDK1/2 - Sgk1. Nous avons montré pour la première fois que Sgk1 est exprimée et phosphorylée dans des conditions basales dans les cellules principales du CCD, mais le mécanisme qui maintient sa phosphorylation n'est pas connu. Ce nouveau rôle pour l'IGF-1 suggère qu'il pourrait être un gène impliqué de susceptibilité au sel. Aussi, l'IGF-1 stimule le transport rénal de Na+ in vivo. De plus, 35 % des patients atteints d'acromégalie (surproduction d'hormone de croissance et d'IGF-1) sont hypertensifs (prévalence plus élevée que la population normale), et des analyses génétiques suggèrent un lien entre le locus du gène de l'IGF-1 et la pression sanguine. RÉSUMÉ GRAND PUBLIC Nos ancêtres se sont génétiquement adaptés pendant des centaines de millénaires à un environnement pauvre en sel (chlorure de sodium) dans la savane équatoriale, où ils consommaient moins de 0,1 gramme de sel par jour. On a commencé à ajouter du sel aux aliments avec l'apparition de l'agriculture (il y a 5000 à 10000 années), et aujourd'hui une diète omnivore, qui inclut des plats préparés, contient plusieurs fois la quantité de sodium nécessaire pour notre fonction physiologique normale (environ 10 grammes par jour). Le corps garde sa concentration constante dans le sang en s'adaptant à une consommation très variable de sel. Pour ceci, il module son excrétion soit directement, soit en sécrétant des hormones régulatrices. Le rein joue un rôle principal dans cette régulation puisque l'excrétion urinaire de sel change selon la diète et peut aller d'une quantité dérisoire à plus de 36 grammes par jour. L'attention qu'on prête au sel est liée à sa relation avec l'hypertension essentielle. Ainsi, le contrôle rénal de l'excrétion de sodium et d'eau est le principal mécanisme dans la régulation de la pression sanguine, et une ingestion excessive de sel pourrait être l'un des facteurs-clé déclenchant l'apparition d'un phénotype hypertensif. L'hormone aldosterone diminue l'excrétion de sodium par le rein en modulant l'expression de gènes qui pourraient être impliqués dans la sensibilité au sel. Dans une lignée cellulaire de rein l'expression du gène TSC22D3, qui se traduit en la protéine Glucocorticoid Induced Leucine Zipper (GILZ), est fortement induite par l'aldosterone. Ceci suggère que GILZ est un médiateur potentiel de l'effet de l'aldosterone, et pourrait être impliqué dans la sensibilité au sel. Pour analyser la fonction de GILZ dans le rein plusieurs approches ont été utilisées. Par exemple, une souris dans laquelle GILZ est spécifiquement inactivé dans le rein est en train d'être produite et permettra l'étude du rôle de GILZ dans l'organisme. De plus, on a montré que GILZ, en conditions basales, n'a pas d'effet direct sur la protéine transportant le sodium à travers la membrane des cellules, le canal sodique épithélial ENaC. On a aussi essayé de trouver des protéines qui interagissent directement avec GILZ utilisant une technique appelée du « double-hybride dans la levure », mais aucun candidat n'a émergé. Des études ont montré que, à de hautes concentrations, l'insuline peut aussi diminuer l'excrétion de sodium. A ces concentrations, elle peut activer son récepteur spécifique, mais aussi le récepteur d'une autre hormone, l'Insulin-Like Growth Factor 1 (IGF-1). En plus, l'infusion d'IGF-1 augmente la rétention rénale de sodium et d'eau, et des mutations du gène codant pour l'IGF-1 sont liées aux différents niveaux de pression sanguine. On a utilisé une nouvelle lignée cellulaire de rein développée dans notre laboratoire, appelée mCCDc11, pour analyser l'importance relative des deux hormones dans l'induction du transport de sodium. On a montré que les deux hormones induisent une augmentation significative du transport de sodium par l'activation de récepteurs à l'IGF-1 et non du récepteur à l'insuline. On a montré qu'à l'intérieur de la cellule leur activation induit une augmentation du transport sodique par le biais du canal ENaC en modifiant la quantité de phosphates fixés sur la protéine Serumand Glucocorticoid-induced Kinase 1 (Sgk1). On a finalement montré que l'IGF-1 et l'aldosterone ont un effet additif sur le transport de sodium en agissant toutes les deux sur Sgk1, qui intègre leurs effets dans le contrôle du transport de sodium dans le rein.

Iowa 58 Viking Road Corridor from U.S. 20 to Greenhill Road in Cedar Falls, Iowa, NHSX-U-58-1(91)--8S-07, 2015

The Proposed Action consists of the improvement of Iowa Highway 58 (IA 58) from U.S. Highway 20 (U.S. 20) north to Greenhill Road in Cedar Falls (Black Hawk County, Iowa). The improvement would include limiting at-grade access to IA 58 by adding one or more interchanges to the corridor which would be located at Viking Road, Greenhill Road, and reconfiguring the U.S. 20 interchange (Figure 1). In order to construct these interchanges and associated ramps, the pavement of IA 58 would be reconstructed. In a couple of locations, the alignment of IA 58 would be shifted.

East 1 St Street Interchange and I-35 Widening, From MP 94.3 to Oralabor Road, Polk County, Iowa, Project # IM-035-4(140)92--13-77, Environmental Assessment and Section 4(f) De Minimis Impact Finding, 2015

From Proposed Action: "The proposed action consists of reconstructing the East 1st Street/I-35 interchange with a Diverging Diamond interchange, widening I-35 from four (4) lanes to six (6) lanes, and widening East 1st Street from four (4) lanes to five (5) lanes from Delaware Avenue to Frisk Drive. The project also proposes to reconstruct the intersections of East 1st Street/Creekview Drive and East 1st Street/Frisk Drive."

One-step nucleic acid amplification (OSNA): a new road to better staging in colon cancer patients?

Introduction: Approximately one fifth of stage I and II colon cancer patients will suffer from recurrent disease. This is partly due to the presence of small nodal tumour infiltrates, which are undetected by standard histopathology using Haematoxylin & Eosin (H&E) staining on one slice and thus may not receive beneficial adjuvant therapy. A new diagnostic, semi-automatic system, called one-step nucleic acid amplification (OSNA), was recently designed for the detection of cytokeratin 19 (CK19) mRNA as a surrogate for lymph node metastases. The objective of the present investigation was to compare the performance of OSNA with both standard H&E as well as intensive histopathologic analyses in the detection of colon cancer lymph node micro- and macro-metastases.Methods: In this prospective study 313 lymph nodes from 22 consecutive stage I - III colon cancer patients were assessed. Half of each lymph node was analysed initially based on one slice of H&E followed by an intensive histologic work-up (5 levels of H&E and immuno-histochemistry staining for each slice), the other half was analysed using OSNA.Results: All OSNA results were available after less than 40 minutes. Fifty-one lymph nodes were positive and 246 lymph nodes negative with both OSNA and standard H&E. OSNA was more sensitive to detect small nodal tumor infiltrates compared to H&E (11 OSNA pos. /H&E neg.). Compared to intensive histopathologic analyses, OSNA had a sensitivity of 94.5% and a specificity of 97.6% to detect lymph node micro- and macro-metastases with a concordance rate of 97.1%. An upstaging due to OSNA was found in 2/13 (15.3%) initially node negative colon cancer patients.Conclusion: OSNA appears to be a powerful and promising molecular tool for the detection of lymph node macro- and micro-metastases in colon cancer patients. OSNA has a similar performance in the detection of micro- and macro-metastases compared to intensive histopathologic investigations and appears to be superior to standard histology with H&E. Since the use of OSNA allows the analysis of the whole lymph node, the problem of sampling bias and undetected tumor deposits due to uninvestigated material will be overcome in the future and OSNA may thus improve staging in colon cancer patients. It is hoped that this improved staging will lead to better patient selection for adjuvant therapy and consecutively improved local and distant control as well as better overall survival.

Effectiveness of Dynamic Messaging on Driver Behavior for Late Merge Lane Road Closures, 2009

Efforts to improve safety and traffic flow through merge areas on high volume/high speed roadways have included early merge and late merge concepts and several studies of the effectiveness of these concepts, many using Intelligent Transportation Systems for implementation. The Iowa Department of Transportation (Iowa DOT) planned to employ a system of dynamic message signs (DMS) to enhance standard temporary traffic control for lane closures and traffic merges at two bridge construction projects in western Iowa (Adair County and Cass County counties) on I-80 during the 2008 construction season. To evaluate the DMS system’s effectiveness for impacting driver merging actions, the Iowa DOT contracted with Iowa State University’s Center for Transportation Research and Education to perform the evaluation and make recommendations for future use of this system based on the results. Data were collected over four weekends, beginning August 1–4 and ending October 16–20, 2008. Two weekends yielded sufficient data for evaluation, one of transition traffic flow and the other with a period of congestion. For both of these periods, a statistical review of collected data did not indicate a significant impact on driver merging actions when the DMS messaging was activated as compared to free flow conditions with no messaging. Collection of relevant project data proved to be problematic for several reasons. In addition to personnel safety issues associated with the placement and retrieval of counting devices on a high speed roadway, unsatisfactory equipment performance and insufficient congestion to activate the DMS messaging hampered efforts. A review of the data that was collected revealed different results taken by the tube counters compared to the older model plate counters. Although variations were not significant from a practical standpoint, a statistical evaluation showed that the data, including volumes, speeds, and classifications from the two sources were not comparable at a 95% level of confidence. Comparison of data from the Iowa DOT’s automated traffic recorders (ATRs) in the area also suggested variations in results from these data collection systems. Additional comparison studies were recommended.

Road Safety Audit for US 52 in Dubuque County from IA 136 to the NCL of Dubuque, 2008

A section of US 52 between Dubuque and Luxemburg, Iowa, was listed in the top 5% of Iowa highways for severe crashes involving impaired drivers and single vehicle run-off-road crashes during 2001–2005, and several crashes have occurred on this roadway near the towns of Luxemburg, Holy Cross, and Rickardsville, Iowa, many on curves. Staff and officials from the Iowa Department of Transportation (Iowa DOT), Iowa State Patrol, Governor’s Traffic Safety Bureau, Federal Highway Administration, Center for Transportation Research and Education Dubuque County, and a retired fire chief met to review crash data and discuss potential safety improvements to U.S. Highway 52. This report outlines the findings and recommendations of the road safety audit team to address the safety concerns on this US 52 corridor and explains several mitigation strategies that the Iowa DOT District 6 Office has selected.

Road Safety Audit for Union County IA 25 from the WCL of Creston to North H-24 Intersection, 2008

In April 2008 a preliminary investigation of fatal and major injury crashes on Iowa’s primary road system from 2001 through 2007 was conducted by the Iowa Department of Transportation, Office of Traffic and Safety. A mapping of these data revealed an apparent concentration of these serious crashes on a section of Iowa 25 north of Creston. Based on this information, a road safety audit of this roadway section was requested by the Office of Traffic and Safety. Iowa 25 is a two-lane asphaltic concrete pavement roadway, 22 ft in width with approximately 6 ft wide granular shoulders. Originally constructed in 1939, the roadway was last rehabilitated in 1996 with a 4-in. asphalt overlay. Except for shoulder paving through a curve area, no additional work beyond routine maintenance has been accomplished in the section. The 2004 traffic map indicates that IA 25 has a traffic volume of approximately 2070 vehicles per day with 160 commercial vehicles. The posted speed is 55 mph. This report contains a discussion of audit team findings, crash and roadway data, and recommendations for possible mitigation of safety concerns for this roadway section.

Road Safety Audit for US 6 from the ECL of Iowa City to the WCL of West Liberty in Johnson and Muscatine Counties, Iowa, 2008

Approximately 13.2 miles of US 6 in eastern Iowa extends from the east corporate limits of Iowa City, Iowa, to the west corporate limits of West Liberty, Iowa. This segment of US 6 is a service level B primary highway, with an annual daily traffic volume varying from 3,480 vehicles per day (vpd) to 5,700 vpd. According to 2001–2007 crash density data from the Iowa Department of Transportation (Iowa DOT), the corridor is currently listed among the top 5% of non-freeway Iowa DOT roads in several crash categories, including crashes involving excessive speed, impaired drivers, single-vehicle run-off-road, and multiple-vehicle crossed centerline. A road safety audit of this corridor was deemed appropriate by the Iowa Department of Transportation’s Office of Traffic and Safety. Staff and officials from the Iowa DOT, Iowa State Patrol, Governor’s Traffic Safety Bureau, Federal Highway Administration, Center for Transportation Research and Education, and several local law enforcement and transportation agencies met to review crash data and discuss potential safety improvements to this segment of US 6. This report outlines the findings and recommendations of the road safety audit team to address the safety concerns on this US 6 corridor and explains several selected mitigation strategies.

Road Safety Audit Report for US 61 from the ECL of Muscatine to the WCL of, 2008

U.S. Highway 61 between Muscatine and Davenport, Iowa, is a four-lane divided section of road approximately 21 miles in length. This section was found to be among the top 5% of Iowa roadways for single-vehicle run-off-road, impaired driver, unbelted driver, and speed-related crashes for the period of 2001 through 2005. A road safety audit of this corridor was deemed appropriate by the Iowa Department of Transportation’s Office of Traffic and Safety. Staff and officials from the Iowa Department of Transportation (Iowa DOT), Iowa State Patrol, Governor’s Traffic Safety Bureau, Federal Highway Administration, Center for Transportation Research and Education, and several local law enforcement and transportation agencies met to review crash data and discuss potential safety improvements to US 61. This report outlines the findings and recommendations of the road safety audit team to address the safety concerns on this US 61 corridor and explains several selected mitigation strategies.

Road Safety Audit for the US 61/Harrison Street and West Locust Street Intersection in Davenport-Scott County, Iowa, 2008

On the October 7 and 8, 2008, a road safety audit was conducted for the intersection of US 61/Harrison Street and West Locust Street in Davenport, Iowa. US 61/Harrison Street is a one-way street and a principal arterial route through Davenport, with three southbound lanes. Locust Street is a four-lane, two-way minor arterial running across the city from west to east. The last major improvement at this intersection was implemented approximately 20 years ago. The Iowa Department of Transportation requested a safety audit of this intersection in response to a high incidence of crashes at the location over the past several years, in view of the fact that no major improvements are anticipated for this intersection in the immediate future. The road safety audit team discussed current conditions at the intersection and reviewed the last seven years of crash data. The team also made daytime and nighttime field visits to the intersection to examine field conditions and observe traffic flow and crossing guard operations with younger pedestrians. After discussing key issues, the road safety audit team drew conclusions and suggested possible enforcement, engineering, public information, and educational strategies for mitigation.

Road Safety Audit for County Road X-37, from the Intersection of G-62 to the East Corporate Limits of Columbus City in Louisa County, Iowa, 2009

A road safety audit was conducted for a 7.75 mile section of County Road X-37 in Louisa County, Iowa. In 2006, the average annual daily traffic on this roadway was found to be 680 vehicles per day. Using crash data from 2001 to 2007, the Iowa Department of Transportation (Iowa DOT) has identified this roadway as being in the highest 5% of local rural roads in Iowa for single-vehicle runoff- road crashes. Considering these safety data, the Louisa County Engineer requested that a road safety audit be conducted to identify areas of safety concerns and recommend low-cost mitigation to address those concerns. Staff and officials from the Iowa DOT, Governor’s Traffic Safety Bureau, Federal Highway Administration, Institute for Transportation, and local law enforcement and transportation agencies met to review crash data and discuss potential safety improvements to this segment of X-37. This report outlines the findings and recommendations of the road safety audit team to address the safety concerns on this X-37 corridor and explain several selected mitigation strategies.